title: Multidrug resistance protein 2 implicates anticancer drug-resistance to sorafenib.
abstract: Sorafenib and sunitinib is a small molecule inhibitor of certain receptor tyrosine kinases, and have improved outcomes for patients with advanced renal cell carcinoma. Inhibitory concentration of 50% cell growth of sorafenib significantly rose to 6.4-fold in a multidrug resistance protein 2 (MRP2) transfected cell line versus control cell line. The concentration of sorafenib was significantly decreased to 74% of control cells after 3 h treatment. In contrast, a tyrosine kinase inhibitor sunitinib did not show alteration of inhibitory concentration of 50% cell growth and accumulation into the cells of MRP2 transfected cells. The present study suggest that sorafenib is a substrate for MRP2, suggesting that MRP2 may implicate drug resistance to sorafenib.
authors.affiliation: Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060–0812, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shibayama
authors.forename: Kou
authors.initials: K
authors.lastname: Nakano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Taguchi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ikeda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugawara
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001557:Benzenesulfonates / Q000378:metabolism* / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000378:metabolism* / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000378:metabolism* / Q000494:pharmacology; D011758:Pyrroles / Q000378:metabolism* / Q000494:pharmacology; D000077157:Sorafenib; D013379:Substrate Specificity; D000077210:Sunitinib; D013552:Swine; D014162:Transfection; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D009536:Niacinamide; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011725:Pyridines; D011758:Pyrroles; D000077157:Sorafenib; D000077210:Sunitinib; D000097202:ATP-Binding Cassette Sub-Family B Member 4